The Role of Vaccine Coverage within Social Networks in Cholera Vaccine Efficacy

Traditional vaccine trial methods have an underlying assumption that the effect of a vaccine is the same throughout the trial area. There are, however, many spatial and behavioral factors that alter the rates of contact among infectious and susceptible individuals and result in different efficacies across a population. We reanalyzed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from cholera vaccines when vaccination rates are high in an individual's social network.We analyzed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse trend for the relation between the level of vaccine coverage in an individual's social network and the incidence of cholera in individual vaccine recipients or placebo recipients after controlling for potential confounding variables.Using bari-level social network ties, we found incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (5.28 cases per 1000 in the lowest quintile vs 3.27 cases per 1000 in the highest quintile; p = 0.037 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's social network were independently related to a reduced risk of cholera.Findings indicate that progressively higher levels of vaccine coverage in bari-level social networks can lead to increasing levels of indirect protection of non-vaccinated individuals and could also lead to progressively higher levels of total protection of vaccine recipients

Nonrandom Distribution of Vector Ticks (Dermacentor variabilis) Infected by Francisella tularensis

The island of Martha's Vineyard, Massachusetts, is the site of a sustained outbreak of tularemia due to Francisella tularensis tularensis. Dog ticks, Dermacentor variabilis, appear to be critical in the perpetuation of the agent there. Tularemia has long been characterized as an agent of natural focality, stably persisting in characteristic sites of transmission, but this suggestion has never been rigorously tested. Accordingly, we sought to identify a natural focus of transmission of the agent of tularemia by mapping the distribution of PCR-positive ticks. From 2004 to 2007, questing D. variabilis were collected from 85 individual waypoints along a 1.5 km transect in a field site on Martha's Vineyard. The positions of PCR-positive ticks were then mapped using ArcGIS. Cluster analysis identified an area approximately 290 meters in diameter, 9 waypoints, that was significantly more likely to yield PCR-positive ticks (relative risk 3.3, P = 0.001) than the rest of the field site. Genotyping of F. tularensis using variable number tandem repeat (VNTR) analysis on PCR-positive ticks yielded 13 different haplotypes, the vast majority of which was one dominant haplotype. Positive ticks collected in the cluster were 3.4 times (relative risk = 3.4, P<0.0001) more likely to have an uncommon haplotype than those collected elsewhere from the transect. We conclude that we have identified a microfocus where the agent of tularemia stably perpetuates and that this area is where genetic diversity is generated

Ecology and Geography of Plague Transmission Areas in Northeastern Brazil

Plague in Brazil is poorly known and now rarely seen, so studies of its ecology are difficult. We used ecological niche models of historical (1966-present) records of human plague cases across northeastern Brazil to assess hypotheses regarding environmental correlates of plague occurrences across the region. Results indicate that the apparently focal distribution of plague in northeastern Brazil is indeed discontinuous, and that the causes of the discontinuity are not necessarily only related to elevation—rather, a diversity of environmental dimensions correlate to presence of plague foci in the region. Perhaps most interesting is that suitable areas for plague show marked seasonal variation in photosynthetic mass, with peaks in April and May, suggesting links to particular land cover types. Next steps in this line of research will require more detailed and specific examination of reservoir ecology and natural history

Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

Yersinia pestis dissemination in a host is usually studied by enumerating bacteria in the tissues of animals sacrificed at different times. This laborious methodology gives only snapshots of the infection, as the infectious process is not synchronized. In this work we used in vivo bioluminescence imaging (BLI) to follow Y. pestis dissemination during bubonic plague. We first demonstrated that Y. pestis CO92 transformed with pGEN-luxCDABE stably emitted bioluminescence in vitro and in vivo, while retaining full virulence. The light produced from live animals allowed to delineate the infected organs and correlated with bacterial loads, thus validating the BLI tool. We then showed that the first step of the infectious process is a bacterial multiplication at the injection site (linea alba), followed by a colonization of the draining inguinal lymph node(s), and subsequently of the ipsilateral axillary lymph node through a direct connection between the two nodes. A mild bacteremia and an effective filtering of the blood stream by the liver and spleen probably accounted for the early bacterial blood clearance and the simultaneous development of bacterial foci within these organs. The saturation of the filtering capacity of the spleen and liver subsequently led to terminal septicemia. Our results also indicate that secondary lymphoid tissues are the main targets of Y. pestis multiplication and that colonization of other organs occurs essentially at the terminal phase of the disease. Finally, our analysis reveals that the high variability in the kinetics of infection is attributable to the time the bacteria remain confined at the injection site. However, once Y. pestis has reached the draining lymph nodes, the disease progresses extremely rapidly, leading to the invasion of the entire body within two days and to death of the animals. This highlights the extraordinary capacity of Y. pestis to annihilate the host innate immune response

Metapopulation structure for perpetuation of Francisella tularensis tularensis

<p>Abstract</p> <p>Background</p> <p>Outbreaks of Type A tularemia due to <it>Francisella tularensis tularensis </it>are typically sporadic and unstable, greatly hindering identification of the determinants of perpetuation and human risk. Martha's Vineyard, Massachusetts has experienced an outbreak of Type A tularemia which has persisted for 9 years. This unique situation has allowed us to conduct long-term eco-epidemiologic studies there. Our hypothesis is that the agent of Type A tularemia is perpetuated as a metapopulation, with many small isolated natural foci of transmission. During times of increased transmission, the foci would merge and a larger scale epizootic would occur, with greater likelihood that humans become exposed.</p> <p>Methods</p> <p>We sampled questing dog ticks from two natural foci on the island and tested them for tularemia DNA. We determined whether the force of transmission differed between the two foci. In addition, we examined the population structure of <it>F. tularensis </it>from ticks by variable number tandem repeat (VNTR) analysis, which allowed estimates of diversity, linkage disequilibrium, and eBURST analysis.</p> <p>Results</p> <p>The prevalence of tularemia DNA in ticks from our two field sites was markedly different: one site was stable over the course of the study yielding as many as 5.6% positive ticks. In contrast, infected ticks from the comparison site markedly increased in prevalence, from 0.4% in 2003 to 3.9% in 2006. Using 4 VNTR loci, we documented 75 different haplotypes (diversity = 0.91). eBURST analysis indicates that the stable site was essentially clonal, but the comparison site contained multiple unrelated lineages. The general bacterial population is evolving clonally (multilocus disequilibrium) and the bacteria in the two sites are reproductively isolated.</p> <p>Conclusion</p> <p>Even within an isolated island, tularemia natural foci that are no more than 15 km apart are uniquely segregated. One of our sites has stable transmission and the other is emergent. The population structure at the stable site is that of a clonal complex of circulating bacteria, whereas the emerging focus is likely to be derived from multiple founders. We conclude that the agent of tularemia may perpetuate in small stable natural foci and that new foci emerge as a result of spillover from such stable sites.</p

Defective Innate Cell Response and Lymph Node Infiltration Specify Yersinia pestis Infection

Since its recent emergence from the enteropathogen Yersinia pseudotuberculosis, Y. pestis, the plague agent, has acquired an intradermal (id) route of entry and an extreme virulence. To identify pathophysiological events associated with the Y. pestis high degree of pathogenicity, we compared disease progression and evolution in mice after id inoculation of the two Yersinia species. Mortality studies showed that the id portal was not in itself sufficient to provide Y. pseudotuberculosis with the high virulence power of its descendant. Surprisingly, Y. pseudotuberculosis multiplied even more efficiently than Y. pestis in the dermis, and generated comparable histological lesions. Likewise, Y. pseudotuberculosis translocated to the draining lymph node (DLN) and similar numbers of the two bacterial species were found at 24 h post infection (pi) in this organ. However, on day 2 pi, bacterial loads were higher in Y. pestis-infected than in Y. pseudotuberculosis-infected DLNs. Clustering and multiple correspondence analyses showed that the DLN pathologies induced by the two species were statistically significantly different and identified the most discriminating elementary lesions. Y. pseudotuberculosis infection was accompanied by abscess-type polymorphonuclear cell infiltrates containing the infection, while Y. pestis-infected DLNs exhibited an altered tissue density and a vascular congestion, and were typified by an invasion of the tissue by free floating bacteria. Therefore, Y. pestis exceptional virulence is not due to its recently acquired portal of entry into the host, but is associated with a distinct ability to massively infiltrate the DLN, without inducing in this organ an organized polymorphonuclear cell reaction. These results shed light on pathophysiological processes that draw the line between a virulent and a hypervirulent pathogen

Flea Diversity as an Element for Persistence of Plague Bacteria in an East African Plague Focus

Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (∼725–1160 m) to higher elevation sites within the focus (∼1380–1630 m). Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence

Finding a Disappearing Nontimber Forest Resource: Using Grounded Visualization to Explore Urbanization Impacts on Sweetgrass Basketmaking in Greater Mt. Pleasant, South Carolina

Despite growing interest in urbanization and its social and ecological impacts on formerly rural areas, empirical research remains limited. Extant studies largely focus either on issues of social exclusion and enclosure or ecological change. This article uses the case of sweetgrass basketmaking in Mt. Pleasant, South Carolina, to explore the implications of urbanization, including gentrification, for the distribution and accessibility of sweetgrass, an economically important nontimber forest product (NTFP) for historically African American communities, in this rapidly growing area. We explore the usefulness of grounded visualization for research efforts that are examining the existence of fringe ecologies associated with NTFP. Our findings highlight the importance of integrated qualitative and quantitative analyses for revealing the complex social and ecological changes that accompany both urbanization and rural gentrification

Plague and Climate: Scales Matter

Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations